The goal of this proposal is to answer important questions about reentry during ventricular fibrillation (VF) that are crucial for improving therapy for sudden cardiac arrest: How is reentry maintained? How are these mechanisms altered by disease or drugs? Can reentry during VF be prevented or halted by pacing. Specific Aim 1: Use electrical mapping to determine if a mother rotor exists in swine. In small hearts a stable, stationary reentrant circuit, called the mother rotor, has been reported in the fastest activating region during VF, called the dominant domain. These findings may not be true in larger hearts. We will perform electrical mapping studies in the larger hearts of pigs to test the hypotheses that (1) a mother rotor is located at the insertion of the posterior LV papillary muscle and (2) the stability of this reentry is affected by drugs and myocardial infarction. Specific Aim 2: Use electrical and optical mapping to optimize pacing techniques to halt or prevent VF. We will use mapping to optimize stimulation waveforms and electrodes which will be used to test the hypotheses that pacing in or near the dominant domain (1) will capture the largest volume of myocardium, (2) can halt reentry and VF, and (3) can prevent VF if performed during the first cycles of an arrhythmia before reentry has developed. Specific Aim 3: Use electrical mapping and monophasic action potential (MAP) recordings to investigate the mechanisms of VF maintenance in humans. We will perform electrical epicardial mapping and epicardial MAP recordings during VF in patients undergoing cardiac surgery and will record from basket electrodes in patients in the clinical electrophysiology laboratory to test the hypotheses that (1) there is a single dominant domain with a VF activation rate faster than in the remainder of the ventricles, (2) conduction block occurs more frequently along the paths of coronary vessels or in regions with a high spatial dispersion of refractoriness, and (3) cardiac disease and drugs alter the organization of VF. Specific Aim 4: Use electrical and MAP recordings to determine if it is possible to capture a portion of the myocardium by pacing during VF in humans. We will test the hypotheses that pacing from the dominant domain (1) captures the maximum amount of tissue during VF and (2) halts the most organized types of VF. [unreadable] [unreadable] [unreadable]